S100A16 knockdown reduces RPN2 expression and inhibits β-catenin/TCF signaling, leading to suppressed metastasis in cervical cancer cells.

S100 calcium-binding protein A16 (S100A16), the most recently identified member of the S100 calcium-binding protein family, has been implicated in various cancers. However, its specific role in cervical cancer remains unclear. In this study, we demonstrated that silencing the S100A16 gene inhibits the migratory ability of HeLa and SiHa cells without affecting their viability. RNA sequencing analysis revealed that S100A16 significantly regulates ribophorin II (RPN2). Furthermore, RPN2 knockdown alone effectively suppressed cell migration and overexpression of S100A16 reversed the inhibition of migration caused by RPN2 silencing. Mechanistically, S100A16 was observed to regulate RPN2 through phosphorylated signal transducer and activator of transcription 3 (p-STAT3), which, in turn, modulated the downstream β-catenin/TCF pathway via phosphorylated GSK3β. An analysis of nuclear and cytosolic protein fractions further indicated that S100A16 silencing reduces the ability of β-catenin to translocate into the nucleus. In conclusion, our research revealed that S100A16 silencing downregulated RPN2 levels through p-STAT3, thereby inhibiting the p-GSK3β/β-catenin/TCF signaling pathway. These findings highlight S100A16 as a potential therapeutic target for cervical cancer.